mp Trump's New Chief of Staff Susie Wiles Discloses His Day One Plans: Report By www.westernjournal.com Published On :: Tue, 12 Nov 2024 14:59:28 +0000 President-elect Donald Trump will begin his second term by putting pieces of his first one back in place, according to incoming White House Chief of Staff Susie Wiles. Wiles made […] The post Trump's New Chief of Staff Susie Wiles Discloses His Day One Plans: Report appeared first on The Western Journal. Full Article News 2024 election Donald Trump Executive order Trump administration U.S. News
mp Flashback: Video of Tom Homan Taking Down AOC Resurfaces, Showing Why Trump Picked Him By www.westernjournal.com Published On :: Tue, 12 Nov 2024 15:27:01 +0000 Shortly after President-elect Donald Trump appointed Tom Homan as “border czar,” the immigration hardliner’s hilarious 2019 smackdown of Democratic Rep. Alexandria Ocasio-Cortez of New York went viral on social media. […] The post Flashback: Video of Tom Homan Taking Down AOC Resurfaces, Showing Why Trump Picked Him appeared first on The Western Journal. Full Article Commentary Alexandria Ocasio-Cortez Border crisis Border security Donald Trump Illegal immigration Trump administration
mp Trump Shares His 10-Step Plan to 'Shatter the Deep State' and It Will Give You Chills By www.westernjournal.com Published On :: Tue, 12 Nov 2024 16:15:13 +0000 To a large extent, President-elect Donald Trump’s winning coalition came together around one absolute truth. In sum, Americans do not have a self-governing constitutional republic if we also have a […] The post Trump Shares His 10-Step Plan to 'Shatter the Deep State' and It Will Give You Chills appeared first on The Western Journal. Full Article Commentary 2024 election Congress Constitution Court Donald Trump Establishment media Foreign Intelligence Surveillance Act Robert F. Kennedy Jr. Supreme Court Term limits Thomas Jefferson Trump administration U.S. News Unconstitutional Washington D.C.
mp Mark Milley Fears He Will Face a Court-Martial When Trump Enters White House By www.westernjournal.com Published On :: Tue, 12 Nov 2024 16:45:43 +0000 Retired Gen. Mark Milley is afraid of retribution. The former chairman of the Joint Chiefs of Staff and a four-star Army general made no bones about his feelings about former […] The post Mark Milley Fears He Will Face a Court-Martial When Trump Enters White House appeared first on The Western Journal. Full Article Commentary 2024 election Afghanistan China Donald Trump Mark Milley Military Politics Ukraine
mp Why Trump Won By www.westernjournal.com Published On :: Tue, 12 Nov 2024 18:18:33 +0000 The election of Donald Trump in 2024 marked a pivotal moment in American politics, a moment that many saw coming from miles away. But what drove this resurgence? Why did […] The post Why Trump Won appeared first on The Western Journal. Full Article Op-Ed 2024 election Democrats Donald Trump Politics
mp Judge Juan Merchan Grants Request from Trump's Legal Team and DA in NY Hush Money Case By www.westernjournal.com Published On :: Tue, 12 Nov 2024 19:24:49 +0000 New York Judge Juan Merchan — who is overseeing President-elect Donald Trump’s business records case — agreed to freeze the case until Nov. 19. There was to be a hearing […] The post Judge Juan Merchan Grants Request from Trump's Legal Team and DA in NY Hush Money Case appeared first on The Western Journal. Full Article News 2024 election Donald Trump New York state Prosecuting Trump
mp Trump Makes His Pick for US Ambassador to Israel as Conflict in Gaza Remains Heated By www.westernjournal.com Published On :: Tue, 12 Nov 2024 20:31:25 +0000 President-elect Donald Trump announced Tuesday that former Arkansas Gov. Mike Huckabee is his pick to be the next U.S. ambassador to Israel. “Mike has been a great public servant, Governor, […] The post Trump Makes His Pick for US Ambassador to Israel as Conflict in Gaza Remains Heated appeared first on The Western Journal. Full Article News 2024 election Donald Trump Israel Mike Huckabee Politics
mp Fired FEMA Worker Reveals Discrimination Against Trump Supporters Was Even Worse Than First Reported By www.westernjournal.com Published On :: Tue, 12 Nov 2024 20:39:18 +0000 Just because you’re paranoid, it doesn’t mean you’re wrong. And for any supporters of President-elect Donald Trump who feel that they’ve been unfairly targeted by the government, but were summarily […] The post Fired FEMA Worker Reveals Discrimination Against Trump Supporters Was Even Worse Than First Reported appeared first on The Western Journal. Full Article Commentary Donald Trump Federal Emergency Management Agency Florida Liberalism Liberals Natural disasters North Carolina Republicans South Carolina Viral
mp Obama-Appointed Federal Judge Temporarily Blocks Ten Commandments Law By www.westernjournal.com Published On :: Tue, 12 Nov 2024 21:41:19 +0000 A Louisiana law that sought to post the Ten Commandments in every schoolroom in the state has been shelved by a federal judge. U.S. District Court Judge John W. deGravelles, […] The post Obama-Appointed Federal Judge Temporarily Blocks Ten Commandments Law appeared first on The Western Journal. Full Article News ACLU Christianity Louisiana U.S. News
mp 'Warrior for Truth': Trump Has Chosen His Next CIA Director, Crediting Pick for 'Exposing Russian Collusion' Hoax By www.westernjournal.com Published On :: Tue, 12 Nov 2024 23:40:01 +0000 President-elect Donald Trump has chosen the next director of the CIA. Trump tapped former Texas congressman and director of national intelligence John Ratcliffe for the job. According to a statement […] The post 'Warrior for Truth': Trump Has Chosen His Next CIA Director, Crediting Pick for 'Exposing Russian Collusion' Hoax appeared first on The Western Journal. Full Article News 2024 election CIA Donald Trump Russia Trump administration U.S. News
mp Report Shows New Front-Runner for Trump's Press Secretary Spot: The Media Should Be Terrified By www.westernjournal.com Published On :: Wed, 13 Nov 2024 00:01:27 +0000 President-elect Donald Trump is reportedly considering lawyer Alina Habba to be the White House press secretary. Habba often spoke to the media while she was on the legal team representing […] The post Report Shows New Front-Runner for Trump's Press Secretary Spot: The Media Should Be Terrified appeared first on The Western Journal. Full Article Commentary 2024 election Donald Trump Kayleigh McEnany Trump administration White House
mp Breaking: Musk, Ramaswamy Officially Join Trump Administration - Their Job Is to Destroy Bureaucracy By www.westernjournal.com Published On :: Wed, 13 Nov 2024 00:59:12 +0000 Pro-Trump businessmen Elon Musk (the richest man in the world) and Vivek Ramaswamy have officially joined the incoming Trump administration. President-elect Donald Trump announced in a statement published Tuesday that […] The post Breaking: Musk, Ramaswamy Officially Join Trump Administration - Their Job Is to Destroy Bureaucracy appeared first on The Western Journal. Full Article News 2024 election Donald Trump Elon Musk Federal government Trump administration U.S. News Vivek Ramaswamy
mp Sport | Makgopa's rise evidence of Broos' Bafana impact: 'You don't want to disappoint such a person' By www.news24.com Published On :: Wednesday Nov 13 2024 05:00:31 Evidence Makgopa wore a sheepish smile when Bafana Bafana coach Hugo Broos showered him with praise before literally patting the forward on the back, making him blush at Dobsonville Stadium. Full Article
mp Commentary: Secret Service Agents Placed on Leave After Trump Assassination Attempt By deneenborelli.com Published On :: Fri, 23 Aug 2024 19:57:50 +0000 Commentary by Susan Crabtree originally published by RealClearPolitics and RealClearWire Three weeks ago, Acting Secret Service Director Ronald Rowe angrily pushed back on senators’ calls to immediately fire or discipline key agents directly responsible for the security failures that led to the assassination attempt against former President Trump at last month’s campaign rally in Butler, … Full Article Commentaries News
mp Commentary: Mayors Can Combat Campus Unrest This School Year By deneenborelli.com Published On :: Tue, 10 Sep 2024 15:06:27 +0000 Commentary by Liz Katz originally published by RealClearPolitics and made available via RealClearWire As a Jewish parent whose daughter graduated from college in May, I witnessed firsthand the violent anti-Israel demonstrations and commencement cancellations that plagued campuses last academic year. While students are excited for their return this fall, I’m gripped by a sense of … Full Article Commentaries News
mp Commentary: Second Assassination Attempt Forces New Reckoning for Trump, Secret Service By deneenborelli.com Published On :: Tue, 17 Sep 2024 14:23:52 +0000 Commentary by Susan Crabtree and Philip Wegmann originally published by The second assassination attempt against former President Donald Trump while he was golfing at one of his Florida courses on Sunday is forcing the United States Secret Service to further tighten security around the Republican presidential nominee and to reevaluate just how much Trump should … Full Article Commentaries News
mp Investigation: Waste of the Day – Walz Campaign Donors Received $15 Billion in State Business By deneenborelli.com Published On :: Tue, 08 Oct 2024 18:13:14 +0000 Investigation by Jeremy Portnoy originally published by RealClearInvestigations and RealClearWire Topline: Minnesota Gov. Tim Walz accepted $890,000 in campaign donations from employees – including C-suite executives – of 434 state vendors between 2019 and 2022, a new report from OpenTheBooks found. Those same companies collected nearly $15 billion in payments from the state between 2019 … Full Article Commentaries News
mp A novel method produces native light-harvesting complex II aggregates from the photosynthetic membrane revealing their role in nonphotochemical quenching [Bioenergetics] By www.jbc.org Published On :: 2020-12-18T00:06:18-08:00 Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment–protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ. Full Article
mp Russia and China in Antarctica: Implications for the Five Eyes By www.chathamhouse.org Published On :: Fri, 02 Dec 2022 14:17:13 +0000 Russia and China in Antarctica: Implications for the Five Eyes 15 December 2022 — 11:00AM TO 12:00PM Anonymous (not verified) 2 December 2022 Online This event explores Russia’s and China’s postions on the Antarctic and offers a critical assessment of their actions in the region. Ever since the 1959 Antarctic Treaty System (ATS), signed at the height of Cold War, Antarctica has remained a demilitarized continent. Today, even though the ATS is not in immediate danger of collapse, Antarctica and the Southern Ocean are no longer insulated from wider geopolitical tension, with China and Russia posing challenges to regional governance. This event also discusses key recommendations for the Five Eyes regarding Russian and Chinese current and future efforts at undermining the ATS and Antarctic governance. The discussion is informed by Mathieu Boulègue’s paper ‘Russia and China in Antarctica and the Southern Ocean: Implications for the Five Eyes’ published by the Sea Power Centre of the Royal Australian Navy. Full Article
mp China is attempting a precarious balancing act By www.chathamhouse.org Published On :: Thu, 09 Mar 2023 15:43:31 +0000 China is attempting a precarious balancing act Expert comment NCapeling 9 March 2023 In its efforts to maintain ties with both Russia and Europe, China is having to wade through conflicting interests and rapidly changing sentiments. Precisely how far China will go in supporting Russia has been one of the most important questions of the war in Ukraine. On 20 February, US secretary of state Antony Blinken warned China may soon provide arms (‘lethal support’) to Moscow. But then, on 24 February – the anniversary of Russia’s invasion – China released a position paper calling for a political settlement to end the conflict, tellingly omitting any mention of its ‘no-limits partnership’ with Russia. China’s goal was to present itself as a neutral mediator. In fact, Beijing’s ties with Russia remain unchanged, even if this relationship has grown more exasperating for Chinese diplomats over the past year. Their job is to continue striking a delicate balance, a task that is becoming increasingly difficult as Russian president Vladimir Putin doubles down on nuclear brinkmanship and reckless rhetoric. Staying out of the Ukraine war With Putin extolling the law of the jungle in its most brutal form, China must be careful not to involve itself too much in the conflict. After all, Russia is clearly losing, and China has high hopes of repairing ties with major European economies. With China focused on moves by the US and its allies in East Asia and the Indo-Pacific, it simply cannot afford sabre-rattling or unrest on its other borders But Putin is of course keen to signal that China has his back. That is why he recently rolled out the red carpet for China’s top diplomat Wang Yi and then alluded to an (unconfirmed) upcoming visit by Chinese president Xi Jinping. Such diplomatic developments allow him to present China’s ambivalent position as, in fact, an endorsement of the invasion. While the costs of aligning with Russia could easily outweigh the benefits for China, one must remember that China’s reasons for maintaining good relations with the Kremlin go beyond the war in Ukraine. For starters, the two countries share a 2,672-mile (4,300-kilometer) border – roughly equivalent to the width of Europe – and the frontier’s exact location was not even finally settled until the beginning of this century, after generations of negotiations that included some 2,000 meetings. Yet to this day, the spectre of the Sino-Soviet split in the 1950s and 1960s looms large on both sides and it is not likely to be exorcised anytime soon. With China focused on moves by the US and its allies in East Asia and the Indo-Pacific, it simply cannot afford sabre-rattling or unrest on its other borders. Moreover, unlike the collective West, China’s foreign policy has always been shaped by interests rather than by values. Even with respect to Russia, the two countries’ bond is based mainly on shared resentment of US hegemony. By deepening their bilateral cooperation in recent years, they have been able to achieve a level of great-power status with which to counterbalance America. Being isolated from the ‘collective West’ is not an attractive option for China, given its hopes of achieving a robust economic rebound after years of the zero-COVID policy But Putin’s misadventure in Ukraine has forced Xi and China’s newly minted Politburo to manage a new set of economic, financial, and political risks. Russia’s war has left the West more firmly united than it has been in years. As China’s relations with the US have reached new lows, Chinese leaders want to avoid also alienating the European Union (EU), which is one of the country’s biggest trading partners. This is why Xi and Chinese diplomats have been so careful not to accept the Kremlin’s talking points in full. Being isolated from the ‘collective West’ is not an attractive option for China, given its hopes of achieving a robust economic rebound after years of the zero-COVID policy. Balancing Europe with the Global South In seeking to keep diplomatic and trade channels open, China’s main tactic has been to reassure European countries that it will use its own ties with Russia to restrain Putin from deploying nuclear weapons. At the same time, China is making a renewed push to strengthen its ties with the Global South where many countries do not see the war in Ukraine in the same stark moral terms as the West does. The emphasis on energy and food security in China’s recent position paper may have struck a chord with developing countries that have been reeling from the war’s negative knock-on effects on their economies. Full Article
mp Mutation of an atypical oxirane oxyanion hole improves regioselectivity of the {alpha}/{beta}-fold epoxide hydrolase Alp1U [Enzymology] By www.jbc.org Published On :: 2020-12-11T00:06:20-08:00 Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an α/β-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (compound 1) and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A Trp-186/Trp-187/Tyr-247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in α/β-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, whereas the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single-crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U and provided a new approach for engineering regioselective epoxide hydrolases. Full Article
mp The endosomal trafficking regulator LITAF controls the cardiac Nav1.5 channel via the ubiquitin ligase NEDD4-2 [Computational Biology] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation. Full Article
mp Business Briefing: Assessing the geopolitical implications of EU AI regulation By www.chathamhouse.org Published On :: Thu, 08 Aug 2024 14:42:14 +0000 Business Briefing: Assessing the geopolitical implications of EU AI regulation 17 September 2024 — 4:00PM TO 5:00PM Anonymous (not verified) 8 August 2024 Chatham House Join us for this critical discussion of how the EU AI Act will shape the world’s approach to the technology. Join us for this critical discussion of how the EU AI Act will shape the world’s approach to the technology Governments, technology companies and civil society groups across the world are now advocating firmer AI regulation. Machine learning algorithms have changed the way we interact with technology and powered much of our online lives for decades: why has this pendulum swung back so far toward greater control, and why now?In 2023 the UK government seized the initiative with its Bletchley AI Safety Summit. The event attempted to address the so called ‘frontier risks’ associated with AI development. Global competition on AI is reflected in AI governance efforts in China, US, the Gulf and beyond. But to date, it is the EU that has led the West in passing AI legislation. The EU AI Act, has separated AI systems into graded risk categories carrying different regulatory requirements, and it remains to be seen whether global AI will feel the Brussels effect.This conversation will cover the following questions:Critics have painted regulation including the AI Act as anti-innovation. Is this a fair assessment?What lessons can we learn from the successes and shortcomings of GDPR?How do we tackle the challenge of low public trust in AI and low public trust in government technology projects, particularly in Western democracies?Does the proliferation of safety institutes, and the AI office, point to the emergence of a new type of technical governance institution? What is its future? Full Article
mp US domestic polarization and implications for the presidential election By www.chathamhouse.org Published On :: Thu, 19 Sep 2024 09:07:13 +0000 US domestic polarization and implications for the presidential election 30 September 2024 — 5:00PM TO 6:00PM Anonymous (not verified) 19 September 2024 Online This webinar explores the rise of polarization amongst the US public and implications for the upcoming election. Domestic polarization has been on the rise in the US in recent years, with Democrats and Republicans moving further away from the centre on key policy issues. As polarization increases, so too do concerns about the state of US democracy and prospects of political violence surrounding the upcoming presidential election. This expert panel discusses key questions including:What are the driving forces of the growing political divide in the US?How far apart are voters on key election issues, from healthcare to immigration to national security?How is partisan polarisation altering the effectiveness of US foreign policy and influencing America’s role in the world? Full Article
mp Reply to Sysel et al.: Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor] By www.jbc.org Published On :: 2020-10-23T00:06:00-07:00 In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,... Full Article
mp Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor] By www.jbc.org Published On :: 2020-10-23T00:06:00-07:00 After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5). Full Article
mp Allosteric activation of proto-oncogene kinase Src by GPCR-beta-arrestin complexes [Enzymology] By www.jbc.org Published On :: 2020-12-04T00:06:06-08:00 G protein–coupled receptors (GPCRs) initiate signaling cascades via G-proteins and beta-arrestins (βarr). βarr-dependent actions begin with recruitment of βarr to the phosphorylated receptor tail and are followed by engagement with the receptor core. βarrs are known to act as adaptor proteins binding receptors and various effectors, but it is unclear whether in addition to the scaffolding role βarrs can allosterically activate their downstream targets. Here we demonstrate the direct allosteric activation of proto-oncogene kinase Src by GPCR–βarr complexes in vitro and establish the conformational basis of the activation. Whereas free βarr1 had no effect on Src activity, βarr1 in complex with M2 muscarinic or β2-adrenergic receptors reconstituted in lipid nanodiscs activate Src by reducing the lag phase in Src autophosphorylation. Interestingly, receptor–βarr1 complexes formed with a βarr1 mutant, in which the finger-loop, required to interact with the receptor core, has been deleted, fully retain the ability to activate Src. Similarly, βarr1 in complex with only a phosphorylated C-terminal tail of the vasopressin 2 receptor activates Src as efficiently as GPCR–βarr complexes. In contrast, βarr1 and chimeric M2 receptor with nonphosphorylated C-terminal tail failed to activate Src. Taken together, these data demonstrate that the phosphorylated GPCR tail interaction with βarr1 is necessary and sufficient to empower it to allosterically activate Src. Our findings may have implications for understanding more broadly the mechanisms of allosteric activation of downstream targets by βarrs. Full Article
mp Disease-associated mutations in inositol 1,4,5-trisphosphate receptor subunits impair channel function [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-25T00:06:30-08:00 The inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), which form tetrameric channels, play pivotal roles in regulating the spatiotemporal patterns of intracellular calcium signals. Mutations in IP3Rs have been increasingly associated with many debilitating human diseases such as ataxia, Gillespie syndrome, and generalized anhidrosis. However, how these mutations affect IP3R function, and how the perturbation of as-sociated calcium signals contribute to the pathogenesis and severity of these diseases remains largely uncharacterized. Moreover, many of these diseases occur as the result of autosomal dominant inheritance, suggesting that WT and mutant subunits associate in heterotetrameric channels. How the in-corporation of different numbers of mutant subunits within the tetrameric channels affects its activities and results in different disease phenotypes is also unclear. In this report, we investigated representative disease-associated missense mutations to determine their effects on IP3R channel activity. Additionally, we designed concatenated IP3R constructs to create tetrameric channels with a predefined subunit composition to explore the functionality of heteromeric channels. Using calcium imaging techniques to assess IP3R channel function, we observed that all the mutations studied resulted in severely attenuated Ca2+ release when expressed as homotetramers. However, some heterotetramers retained varied degrees of function dependent on the composition of the tetramer. Our findings suggest that the effect of mutations depends on the location of the mutation in the IP3R structure, as well as on the stoichiometry of mutant subunits assembled within the tetrameric channel. These studies provide insight into the pathogenesis and penetrance of these devastating human diseases. Full Article
mp Brexit: Implications for EU–China Relations By www.chathamhouse.org Published On :: Wed, 10 May 2017 09:30:14 +0000 Brexit: Implications for EU–China Relations Research paper sysadmin 10 May 2017 For Beijing, the EU–China relationship will take priority over UK–China ties – with China’s relative focus on Germany becoming even more significant. — Containers are loaded onto a freight train at a depot in Corringham, east of London, en route to Yiwu, China, on 10 April 2017. Photo: Getty Images. Summary The extent of current UK relations with China means that Brexit will notably reduce the scale and diversity of overall EU–China economic and commercial interactions. But the impact will vary across different areas. In policy terms, liberal voices on economic policy towards China will be somewhat weaker among the post-Brexit EU27. Brexit will not be the most important factor determining the future level of strategic coherence in EU policy towards China. The impact on post-Brexit EU27 trade with China will be felt both in the volume of trade and its composition. Following Brexit the EU will no longer be China’s largest trading partner. There will be some relative shift in Chinese investment in Europe away from the UK, though over time the impact of Europe-wide policy approaches to Chinese investment will have more impact than Brexit per se. EU–China educational exchanges will be weakened after Brexit, but inbound Chinese tourism will be less affected by Brexit. By 2025, the EU will have compensated for Brexit’s impact in some areas, but much depends on the EU’s own trajectory over the next decade. For Beijing, the EU–China relationship will take priority over UK–China ties. Within the EU, China’s relative focus on Germany will be even more significant. 2017-05-11-brexit-eu-china-summers-final (PDF) Full Article
mp Belt and Road Is Not a (Completely) Closed Shop By www.chathamhouse.org Published On :: Thu, 22 Mar 2018 09:47:39 +0000 Belt and Road Is Not a (Completely) Closed Shop Expert comment sysadmin 22 March 2018 Though the infrastructure initiative will continue to be led in many places by Chinese investment, where there are benefits of scale, effectiveness and risk management, outside participation will be welcome. — Chinese Foreign Minister Wang Yi at the Belt and Road Forum in Yanqi Lake in May 2017. Photo: Getty Images. First announced in 2013, President Xi Jinping’s Belt and Road Initiative promises, at a minimum, to improve infrastructure and connectivity between China and the rest of Eurasia. Any bold plan to finance infrastructure on a large-scale across so many low-income economies deserves a sympathetic ear and a positive reception. But many wonder how large the role can be for non-Chinese players in what is clearly an initiative of the Chinese government. So far, Chinese state and policy banks account for the overwhelming majority of the financing – and this money then flows to Chinese enterprises, mainly state-owned. One study found that 89% of the work went to Chinese contractors on China-funded projects. Yet, recently in Paris, Chinese Foreign Minister Wang Yi said the Belt and Road was a ‘sunshine initiative’ that was open and for all to benefit from. He declared that there were to be ‘no backroom deals. There is openness and transparency.’ The Belt and Road Initiative will ‘respect international rules’ and ‘will run according to market rules’.There are some notable instances of Belt and Road projects changing to conform more to international rules as they develop. For example, work on the Belgrade–Budapest high speed rail link originally ran into problems. Contracts were allegedly awarded to Chinese companies without following the EU-mandated competitive procurement processes. Now, the most recent round of contracts is to be awarded by tender.Such a switch perhaps does not herald the unrestricted ‘market rules’ that Wang speaks of, but it does highlight that China is willing to turn Belt and Road towards openness in certain instances. These will be cases where it clearly brings benefits for China – but also where private sector players can be convinced of good commercial returns. These benefits are most likely to lie in three areas: scale and access, effectiveness and risk management.Mutual benefitsFirstly, scale and access. Belt and Road can achieve greater scale if additional financing comes in alongside the current Chinese state and policy bank lending. This can come both by working together with multilateral institutions and with private sector institutions. This will in turn require defining projects or structuring financing with attractive risk-return trade-offs. In some cases, this will be feasible – in others not. Getting bigger also necessitates initiating meaningful Belt and Road activity in more countries. As the Belgrade–Budapest rail experience has shown, approaches vary in terms of competitive tendering requirements and consideration of non-Chinese bidders. An approach that works in, say, Tajikistan, may not be effective in Poland. This is a pragmatic recognition of context that is quite separate from debates on what the ‘right’ approach to these standards should be. Both these elements suggest that a more open Belt and Road will be a larger and more far-reaching one.Secondly, effectiveness. Despite extensive experience building infrastructure within China, many Chinese companies are much less familiar operating outside of China. Western, Japanese and Korean companies can bring their own experience to the table and help the success of these projects. By doing so, they also put competitive pressure on Chinese companies to improve and upgrade, while providing opportunities to learn. This in turn creates a stronger, more productive Chinese economy.Beyond physical hardware, the ‘software’ is also critical to success. Again foreign companies have much to contribute. Areas such as maintenance, training, legal and accounting services are all in demand. Indeed, many such British and other companies are already actively engaged in working on projects with Chinese companies to help in these areas.Finally, risk management. Beyond the usual project management risk of large projects, Belt and Road brings additional challenges. Many countries have weak governance, internal divisions and security issues, all within distinctively different cultures and traditions. Chinese companies with little experience of local conditions will struggle. Going it alone may provide what is an illusion of control, but exposure to social and political dynamics can rebound on China in unexpected ways.Cooperating with others who have a history of in-country experience is a way to manage these risks. Examples would include British and Chinese cooperation both at company and governmental level in engaging in particular African countries, in partnership with the relevant country government.Mixed systemMechanisms that encourage competitive choices and restrain corruption are positive, but mechanisms that slow decision-making to a crawl also prevent countries from getting benefits of infrastructure projects. Conversely, continuing along the current path of Chinese-led investment does have some clear attractions in certain settings, at least to those directly involved. It combines the ability of Chinese policy banks to provide large-scale funding in even high-risk environments with the relevant experience and production capacity of Chinese state-owned businesses. It allows for government-to-government deals, pragmatic negotiations and all-encompassing accords, at times out of the public eye. In many cases, it is hard to make a commercial case for the investments.But in cases where there is mutual benefit, engagement and will, there will be a role for international partnerships. Full Article
mp Virtual Roundtable: The Economic Implications of COVID-19 on Asia By www.chathamhouse.org Published On :: Fri, 27 Mar 2020 16:35:01 +0000 Virtual Roundtable: The Economic Implications of COVID-19 on Asia 2 April 2020 — 11:00AM TO 12:00PM Anonymous (not verified) 27 March 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE The COVID-19 pandemic is likely to have a damaging economic impact on Asia, potentially the most serious since the financial crisis two decades ago. While early estimates suggest that a recession is inevitable, differing countries in Asia are generally deploying modest fiscal and monetary measures. This is true even in China, compared with the ‘whatever it takes’ approach pursued by Europe and America. How effective will these measures be in reviving growth and in easing the pain, particularly on the poor in developing countries in Asia? Is Asia witnessing a sudden but temporary halt in economic activity rather than a prolonged slowdown? At this virtual roundtable, the speakers will consider the likelihood of a recovery for trade in the region and will explore what lessons can be learned from countries like Singapore, who seem to be successfully managing the health and economic aspects of COVID-19. This event is online only. After registering, you will receive a follow-up confirmation email with details of how to join the webinar. Full Article
mp What are the lasting impacts of the AUKUS agreement? By www.chathamhouse.org Published On :: Mon, 15 Aug 2022 21:32:19 +0000 What are the lasting impacts of the AUKUS agreement? Interview LJefferson 15 August 2022 Drawing on their International Affairs article, Jamal Barnes and Samuel Makinda outline the effect of AUKUS on Australia-France relations and the liberal order. Almost a year after the surprise announcement of the AUKUS treaty, its full diplomatic implications are still being understood. The security cooperation agreement between Australia, the US and the UK caused outrage in France and was a notable source of discord between states that see themselves as defenders of the liberal international order. In this interview Jamal Barnes and Samuel Makinda discuss their recent article in International Affairs and assess the effect of the agreement on relationships between its signatories and France and the EU, the potential for reconciliation in the treaty’s aftermath, as well as the implications it has for trust in world politics. What was the AUKUS treaty and why did Australia sign it? The AUKUS treaty is an agreement between Australia, the US and the UK. Signed in 2021, it facilitates cooperation on security issues in the Indo-Pacific between the three countries – specifically, it concerns the sharing of ‘military capabilities and critical technologies, such as cyber, artificial intelligence, quantum technologies, and undersea domains’. A key aspect is that Australia will purchase nuclear-fuelled submarines from either the US or UK. Australia decided to purchase nuclear-powered submarines – and reneged on its 2016 agreement to purchase French-built diesel-propelled submarines – because it believed that the French-made submarines were no longer fit for purpose. The AUKUS agreement reflects the increased attention that the US, UK and Australia are paying to the Indo-Pacific and their commitment to constraining China’s exercise of power in the region. However, the agreement is about more than submarines. Although Australia, the UK and US argue that AUKUS is designed to defend the rules-based international order and help ‘preserve security and stability in the Indo-Pacific’, AUKUS has been largely seen as a response to the rise of China and its military activities in the region. The AUKUS agreement reflects the increased attention that the US, UK and Australia are paying to the Indo-Pacific and their commitment to constraining China’s exercise of power in the region. What were the effects of the AUKUS treaty on relations between Australia and France? It led to a serious diplomatic rift. Australian officials, including former Prime Minister Morrison, had visited President Macron in France and told him nothing about AUKUS. Morrison had assured Macron in June 2021 while former Australian foreign and defence ministers had assured their French counterparts that Australia was fully committed to the purchase of French submarines just two weeks before the announcement of AUKUS. France was not only left out of talks but was also betrayed by a country it considered a close ally. When French officials found out about AUKUS on the day it was announced on 15 September 2021, they declared publicly that they had been betrayed and stabbed in the back. Not only had France built its relationship with Australia on trust, but its relationship was more than just about submarines. It was designed to be central to France’s 50-year engagement strategy in the Indo-Pacific. However, France was not only left out of talks but was also betrayed by a country it considered a close ally. France responded by temporarily recalling its ambassador and stated that it would ‘redefine’ its relationship with Australia. It did not say that it would not work with Australia, but rather downgraded its relationship to one where it would only do so on a case-by-case basis. In your article you mention that the AUKUS treaty was seen as a betrayal of trust by France in particular. Why use the word ‘betrayal’? The word betrayal is accurate because Australia’s actions went beyond simply cancelling a business contract. Australia breached France’s trust. Not all agreements involve trust. Some are driven by self-interest while others are simply legal contracts. When these agreements are broken, the usual response is feelings of disappointment and a belief that one party is unreliable and has not lived up to its end of the agreement. However, when diplomatic partnerships involve trust, they often contain an emotional element. A key element of trust is that one party makes itself vulnerable to another in the expectation that neither party will take advantage. When that trust is breached, the response is different from a breach of contract. It involves feelings of betrayal as deeper emotional factors are involved. This could be seen in President Macron’s anger, and his and other French officials’ willingness to publicly call Prime Minister Morrison a liar who had stabbed France in the back. If the previous France-Australia agreement was simply a legal contract, it would have been difficult to explain the emotional element of this diplomatic fallout. How did the signing of the AUKUS treaty affect wider relations between members of AUKUS and EU member states? The EU, like France, felt betrayed by the AUKUS announcement. Despite being a key ally of the US, Australia, and the UK, it was left out of AUKUS discussions, and was not aware of the agreement until it was announced in the media. For the EU, this was the latest in a long line of recent policy betrayals that had left it uncertain if it could trust key allies on important issues. What made this worse was that the EU was in the process of announcing its Indo-Pacific strategy, which was characterized as ‘maybe one of the [EU’s] most important geopolitical documents’ by High Representative for Foreign and Security Affairs, Josep Borrell. For the EU, this was the latest in a long line of recent policy betrayals that had left it uncertain if it could trust key allies on important issues. The result was greater calls from within the EU to more forcefully pursue ‘strategic autonomy’, meaning a more assertive and independent EU foreign policy. Do betrayals of trust affect the health of the liberal international order? Yes, they can. While it is common for leaders in liberal democracies to lie to their own people, lying to the leaders of other countries can have serious repercussions for the norms, rules and institutions of international society. A key aspect of international society is the ‘presumption of trust’ that facilitates legal compliance and diplomatic cooperation. Without this presumption it is difficult for states to engage in long term partnerships or have confidence that diplomatic agreements will be upheld. In our article, we highlight how Australia’s violation of a particular norm, that agreements must be kept, has undermined this presumption of trust. This norm not only helps build trust between states, but also contributes to the maintenance of international order by helping to support the presumption of trust in international society. Full Article
mp The interconnected impacts of the Iraq war By www.chathamhouse.org Published On :: Wed, 22 Mar 2023 15:43:28 +0000 The interconnected impacts of the Iraq war Expert comment LJefferson 22 March 2023 Relying on weak intelligence for invading Iraq has had a negative impact on US and UK credibility with several consequences that persist to this day. 20 years on from the fateful decision to invade Iraq, it is generally accepted that the US and UK governments overstated the evidence available for them to justify military action. The central claim to defend invading Iraq was that the country had continued its illicit nuclear weapons programme and had retained illegal stockpiles of biological and chemical weapons. None of these claims supported an imminent threat justification nor could any hidden caches of WMD be found by the US Iraq Survey Group after the invasion. In the US, President George W. Bush and Vice President Dick Cheney hinted at additional evidence which could not be shared publicly to suggest that if only people knew what the government knew, they would agree that Iraq posed a significant threat to the West and needed to be disarmed. In the UK, the Blair government acted similarly, focusing on a narrow interpretation of the evidence provided by the intelligence services and ignoring many of the dire warnings offered by academics and other experts. The Chilcot Inquiry found that the Blair government greatly exaggerated the threat Iraq posed to the UK, and that government arguments were based on the prime minister’s personal beliefs, as well as his promise to President Bush to support the US invasion. Relying on inadequate information and a biased analysis for invading Iraq has had a negative impact on US and UK credibility in the international security policy environment and domestically with ramifications that persist to this day. Impacts on soft power and trust The invasion had an impact on US and UK soft power due to negative perceptions of the decision to go to war and the competence of the UK and US: public opinion polling by the Pew Center showed that perceptions of the US declined significantly as a result of the invasion of Iraq, especially in the Middle East and Central Asia. This is undoubtedly a challenge for the US, but arguably an even bigger challenge for the UK, which due to its size and power relies much more on diplomacy and coalition-building in order to achieve its goals within various international treaty frameworks. The accuracy of the US/UK intelligence on Russia’s invasion, coupled with their sharing it openly, may well have restored faith in their capabilities and analysis. Over nearly two decades, the US and the UK no longer seemed to enjoy the same foundation of trust, even with close allies, as they did previously. This changed in February 2022. Towards the end of 2021, both the US and the UK were sounding the alarm about an impending Russian invasion of Ukraine based on information and analysis from their intelligence services. Despite the amassing of Russian troops, tanks and artillery on the border clearly visible from the air and by satellite imagery, several allies remained unconvinced until the invasion happened. This was in part due to their own assessments which indicated that Russia would stop short of an invasion, and in part because allies were unwilling to take US and UK statements on faith, without being able to assess the information themselves. US officials found this frustrating as it meant that NATO and the EU were slower off the mark with support for Ukraine than they might otherwise have been. However, the accuracy of the US/UK intelligence on Russia’s invasion, coupled with their sharing it openly, may well have restored faith in their capabilities and analysis. A more open approach to intelligence Over the last few years, there seems to have been a change in accepted practice regarding sharing and using intelligence. The UK Ministry of Defence has taken a much more open approach to intelligence in the war in Ukraine, sharing the most recent defence information publicly in order to counter Russian disinformation. This is a positive step to ensure that intelligence can be discussed and assessed critically. Being more open about secret intelligence may also be linked to the increasing capabilities of open-source intelligence (OSINT). Non-governmental and international organizations and the media all now have access to data from, for example, imaging satellites and can independently verify information coming from governments. Perceived double standards A reduction of trust in US and UK intelligence was not the only impact of the invasion of Iraq. Russia and China have repeatedly called out the US and UK for acting without a second UN Security Council mandate. Putin uses the decision to invade Iraq, as well as the NATO humanitarian intervention in Kosovo, to justify Russia’s actions in Crimea. He invokes parallel language to spread disinformation about a ‘responsibility to protect life’ of the (‘ethnically Russian’) Crimean population. Russia has also repeatedly used the WMD trope to create false narratives around Ukrainian biosecurity laboratories to justify Russian military actions against Ukraine. Putin uses the decision to invade Iraq, as well as the NATO humanitarian intervention in Kosovo, to justify Russia’s actions in Crimea. Deciding to invade Iraq under what turned out to be a false pretext has weakened the application of the international rule of law and has led to a perceived double standard whereby powerful states can use UN processes in their favour, or completely disregard them if they do not deliver their goals. As the Chilcot Inquiry found, there was very little preparation for the post-invasion period either in the US or the UK. Confirmation bias led not only to trusting shaky intelligence but also to believing in a best-case scenario and a ‘relatively benign security environment’ once the invasion had prevailed. Mismanaging the country’s occupation afterwards also led to the perception that the UK and US are less competent than projected. Problems for the international order The Iraq War has left many smaller and medium-sized states outside Europe and North America with the impression that powerful states are not committed to an equitable international system and instead will bend the rules to suit them while nonetheless holding other states to account. This dynamic poses a serious problem for the international system. It opens the door to ‘whataboutism’ in Russia’s false justifications for invading Ukraine and undermines faith in international law, destabilizing the international order in the longer term. Beyond the immediate challenges of dealing with the war in Ukraine, reforming and strengthening the international order to make it more equitable will be one of the most significant challenges the US and UK will face over the next decade. A trust deficit Domestically, for already disappointed citizens, the deceit over intelligence it is yet another piece of evidence which suggests that their government is not trustworthy and may not have their best interests at heart. This has profound implications for US and UK democracies, making it harder for governments to counter citizens’ susceptibilities to disinformation campaigns. Full Article
mp Molecular Composition of IMP1 Ribonucleoprotein Granules By www.mcponline.org Published On :: 2007-05-01 Lars JønsonMay 1, 2007; 6:798-811Research Full Article
mp High Resolution Clear Native Electrophoresis for In-gel Functional Assays and Fluorescence Studies of Membrane Protein Complexes By www.mcponline.org Published On :: 2007-07-01 Ilka WittigJul 1, 2007; 6:1215-1225Research Full Article
mp The Proteome of the Mouse Photoreceptor Sensory Cilium Complex By www.mcponline.org Published On :: 2007-08-01 Qin LiuAug 1, 2007; 6:1299-1317Research Full Article
mp Comparative Proteomic Analysis of Eleven Common Cell Lines Reveals Ubiquitous but Varying Expression of Most Proteins By www.mcponline.org Published On :: 2012-03-01 Tamar GeigerMar 1, 2012; 11:M111.014050-M111.014050Special Issue: Prospects in Space and Time Full Article
mp Complementary Profiling of Gene Expression at the Transcriptome and Proteome Levels in Saccharomyces cerevisiae By www.mcponline.org Published On :: 2002-04-01 Timothy J. GriffinApr 1, 2002; 1:323-333Research Full Article
mp Toward a Comprehensive Atlas of the Physical Interactome of Saccharomyces cerevisiae By www.mcponline.org Published On :: 2007-03-01 Sean R. CollinsMar 1, 2007; 6:439-450Research Full Article
mp A Proteomic Analysis of Human Cilia: Identification of Novel Components By www.mcponline.org Published On :: 2002-06-01 Lawrence E. OstrowskiJun 1, 2002; 1:451-465Research Full Article
mp A Tandem Affinity Tag for Two-step Purification under Fully Denaturing Conditions: Application in Ubiquitin Profiling and Protein Complex Identification Combined with in vivoCross-Linking By www.mcponline.org Published On :: 2006-04-01 Christian TagwerkerApr 1, 2006; 5:737-748Research Full Article
mp Comparison of Label-free Methods for Quantifying Human Proteins by Shotgun Proteomics By www.mcponline.org Published On :: 2005-10-01 William M. OldOct 1, 2005; 4:1487-1502Research Full Article
mp The Paragon Algorithm, a Next Generation Search Engine That Uses Sequence Temperature Values and Feature Probabilities to Identify Peptides from Tandem Mass Spectra By www.mcponline.org Published On :: 2007-09-01 Ignat V. ShilovSep 1, 2007; 6:1638-1655Technology Full Article
mp Exponentially Modified Protein Abundance Index (emPAI) for Estimation of Absolute Protein Amount in Proteomics by the Number of Sequenced Peptides per Protein By www.mcponline.org Published On :: 2005-09-01 Yasushi IshihamaSep 1, 2005; 4:1265-1272Research Full Article
mp Stable Isotope Labeling by Amino Acids in Cell Culture, SILAC, as a Simple and Accurate Approach to Expression Proteomics By www.mcponline.org Published On :: 2002-05-01 Shao-En OngMay 1, 2002; 1:376-386Research Full Article
mp Building a Fantasy Army — Environment & Society By mythicscribes.com Published On :: Sun, 30 May 2021 19:26:53 +0000 This article is by Toni Šušnjar. Warfare and military are an integral part of much of ancient and medieval fantasy. This is no surprise: warfare was a key element in development of society and of history, and much of mythology is also about it. As such, it is difficult for fantasy writers and readers alike to avoid war and military matters in general. And if you are going to do something, try to do it well. Army does not spring from the ground like the spartoi of Jason. Environment and Geography Environmental conditions include terrain, climate and resources. All three influence how an army will fight and which weapons it will use. Terrain can be highly varied, but I will divide it into three categories: mountainous, rolling hills and flat. Mountains and forests – and especially forested mountains – are conductive to infantry warfare. Depending on other conditions (such as society, climate etc.), this can mean either light infantry with focus on ambushes, raiding and guerilla warfare; or heavy infantry, with focus on direct confrontation. Both of these were, at different points, in evidence in Spain and Greece. Continue reading Building a Fantasy Army — Environment & Society at Mythic Scribes. Full Article World Building Building a Fantasy Army
mp Building a Fantasy Army — Strategy & Organization By mythicscribes.com Published On :: Sun, 06 Jun 2021 20:13:34 +0000 This article is by Toni Šušnjar. Strategy and Enemies The structure of an army will depend on the strategy, as strategy will determine the army’s role and tasks. A state which carries out expansion through outright territorial conquest will have large numbers of heavy infantry, combat engineers and artillery, and possibly some heavy cavalry as well (e.g. Roman Empire, 10th century Byzantine Empire). If conquest is done by slowly destroying an opponent’s economic and social structures through constant raiding (such as chevauchee or razzia / ghazw), then majority of the army will be light cavalry, with some heavy cavalry support (e.g. Seljuk and Ottoman Empires), and light infantry will be used if terrain is unsuitable for cavalry. If a state is defending against cavalry raids, then light cavalry will be dominant (e.g. 15th century Hungary), whereas heavy cavalry will predominate if enemy raiders are primarily infantry. If enemy armies are too powerful to face in the field, light and heavy cavalry will be used to harass the invading army and cut off its supplies and foraging. In terrain unsuitable for cavalry operations, heavy infantry will be used instead. Raiding — as a strategy — is generally preferred against a peer opponent, especially if a state cannot have a developed logistical support system. Continue reading Building a Fantasy Army — Strategy & Organization at Mythic Scribes. Full Article World Building Building a Fantasy Army
mp Building a Fantasy Army — Recruitment & Logistics By mythicscribes.com Published On :: Sat, 19 Jun 2021 23:42:51 +0000 This article is by Toni Šušnjar. Recruitment and Numbers The most basic style of recruitment is that of a local militia – rural or urban – where a portion or all of the free men take up arms. Militiamen are usually not highly trained, but they make up for lack of training with motivation: fleeing not only carries social stigma, but is also harshly punished. As such, militias were more effective than what would be expected of “civilians in arms”. Militias almost always depended on relatively cheap and easy to use weapons, though urban militias might have access to more expensive weapons – such as hoplite panoply or crossbows. Tribal militias typically used weapons that were also used for hunting and sport. Peasant levy however was only ever used in a support and harassment role, and often had weapons modified from agricultural implements. Only urban militias could have heavy equipment. A common disadvantage of militia armies is the inability to deploy over long distances and time-frames due to soldiers having a day job; thus, focus on long-term warfare (be it conquest or defence) typically brings about the professionalization of the army. This also means that militias are best used in cases with high political fragmentation – such as city-states. Continue reading Building a Fantasy Army — Recruitment & Logistics at Mythic Scribes. Full Article World Building Building a Fantasy Army
mp Building a Fantasy Army — Weapons & Tactics By mythicscribes.com Published On :: Thu, 01 Jul 2021 21:47:58 +0000 This article is by Toni Šušnjar. In Antiquity and early the Middle Ages, the main weapon was the spear. Only a few exceptions appeared: Roman legions, which used javelins instead, and Macedonian pike phalanx with its sarissa. In the later Middle Ages, the main weapon could be a pike or a polearm (such as polehammer, poleaxe, halberd etc.), before the pike made its return in early modernity. Ranged weapons were not used to cause casualties, but rather to inconvenience the enemies and break up their formation. Weapons and tactics will adapt to each other, as well as to the terrain and the enemies faced – but adaptations will be done within the boundaries of the society. A society without a significant tradition of horse archery will not counter horse archers with their own, but rather with foot archers. Horse archery was important for nomadic societies, because they could not afford the casualties which resulted from the shock and attrition tactics of the settled societies. Weapons and armour likewise have a relationship, but since armour is the more difficult to produce of the two, it is developments in armour which typically drive the adaptation of weapons, rather than the other way around. Continue reading Building a Fantasy Army — Weapons & Tactics at Mythic Scribes. Full Article World Building Building a Fantasy Army
mp Differential compartmental processing and phosphorylation of pathogenic human tau and native mouse tau in the line 66 model of frontotemporal dementia [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-12-25T00:06:31-08:00 Synapse loss is associated with motor and cognitive decline in multiple neurodegenerative disorders, and the cellular redistribution of tau is related to synaptic impairment in tauopathies, such as Alzheimer's disease and frontotemporal dementia. Here, we examined the cellular distribution of tau protein species in human tau overexpressing line 66 mice, a transgenic mouse model akin to genetic variants of frontotemporal dementia. Line 66 mice express intracellular tau aggregates in multiple brain regions and exhibit sensorimotor and motor learning deficiencies. Using a series of anti-tau antibodies, we observed, histologically, that nonphosphorylated transgenic human tau is enriched in synapses, whereas phosphorylated tau accumulates predominantly in cell bodies and axons. Subcellular fractionation confirmed that human tau is highly enriched in insoluble cytosolic and synaptosomal fractions, whereas endogenous mouse tau is virtually absent from synapses. Cytosolic tau was resistant to solubilization with urea and Triton X-100, indicating the formation of larger tau aggregates. By contrast, synaptic tau was partially soluble after Triton X-100 treatment and most likely represents aggregates of smaller size. MS corroborated that synaptosomal tau is nonphosphorylated. Tau enriched in the synapse of line 66 mice, therefore, appears to be in an oligomeric and nonphosphorylated state, and one that could have a direct impact on cognitive function. Full Article